PHARMACOLOGICAL CHARACTERIZATION OF MUSCARINIC RECEPTORS IN RABBIT ISOLATED IRIS SPHINCTER MUSCLE AND URINARY-BLADDER SMOOTH-MUSCLE

1 The pharmacological characteristics of muscarinic receptors in the r abbit iris sphincter muscle were studied and compared to Mg receptors in rabbit urinary bladder smooth muscle. 2 (+)-Cis-dioxolane induced c oncentration-dependent contractions of the iris sphincter muscle (pEC( 50) = 6.41 +/- 0.10, E-max = 181 +/- 17 mg, n = 38) and urinary bladde r smooth muscle (pEC(50) = 6.97 +/- 0.04, E-max = 4.28 +/- 0.25 g, n = 54). These contractions were competitively antagonized by a range of muscarinic receptor antagonists (pK(B) values are given for the iris s phincter muscle and the bladder smooth muscle, respectively): atropine (9.30 +/- 0.07 and 9.40 +/- 0.04), AQ-RA 741 (6.35 +/- 0.04 and 6.88 +/- 0.03), darifenacin (9.56 +/- 0.05 and 9.12 +/- 0.05), methoctramin e (5.75 +/- 0.07 and 5.81 +/- 0.06), oxybutynin (8.10 +/- 0.09 and 8.5 9 +/- 0.06), pirenzepine (6.79 +/- 0.05 and 6.89 +/- 0.04), secoverine (7.54 +/- 0.05 and 7.66 +/- 0.05), p-F-HHSiD (7.55 +/- 0.09 and 7.50 +/- 0.05) and zamifenacin (8.69 +/- 0.10 and 8.36 +/- 0.06). A signifi cant correlation between the pK(B) values in the bladder and the pK(B) values in the iris was obtained. 3 In both tissues, the pK(B) values correlated most favorably with pK(i) values for these compounds at hum an recombinant muscarinic m3 receptors. A reasonable correlation was a lso noted at human recombinant muscarinic m5 receptors given the poor discriminative ability of ligands between m3 and m5 receptors. 4 Overa ll, the data from this study suggest that the muscarinic receptors med iating contraction of the rabbit iris sphincter muscle and urinary bla dder smooth muscle are similar and equate most closely with the pharma cologically-defined muscarinic M3 receptor.